http://repub.eur.nl/res/aut/34771/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/26006/ 2011-04-01T00:00:00Z Background  Methotrexate and fumarates are effective systemic therapies for moderate to severe psoriasis according to the European S3 guidelines. Objectives  We conducted a randomized controlled trial comparing the effectiveness and the adverse events of methotrexate and fumarates. Methods  Sixty patients with moderate to severe psoriasis vulgaris were randomly assigned to treatment for 16 weeks with either methotrexate (30 patients; 15 mg per week) or fumarates (30 patients; 30 mg, followed by 120 mg according to a standard progressive dosage regimen) and were followed up for 4 weeks. The primary endpoint with respect to the efficacy was the difference in mean change from baseline in Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment. The study was powered to detect a difference of five points. Analyses were by intention to treat. Results  Six patients were excluded because five were not eligible and one withdrew consent. Two patients in the methotrexate group and one in the fumarate group dropped out during the 12 weeks of treatment because of nonappearance at the outpatient clinic. In total, 25 patients in the methotrexate group and 26 in the fumarate group were evaluated in the primary analysis. After 12 weeks of treatment, the mean ± SD PASI decreased from 14·5 ± 3·0 at baseline to 6·7 ± 4·5 in the 25 patients treated with methotrexate, whereas it decreased from 18·1 ± 7·0 to 10·5 ± 6·7 in the 26 patients treated with fumarates. After adjustment for baseline values, the absolute difference (fumarates minus methotrexate) in the mean values at 12 weeks was 1·4 (95% confidence interval −2·0 to 4·7; P  =   0·417). Conclusions  In this randomized trial methotrexate and fumarates were found to be equally effective in the treatment of patients with moderate to severe psoriasis. No serious or irreversible adverse events were observed in any of the patients. http://repub.eur.nl/res/pub/25379/ 2009-11-01T00:00:00Z Context: Von Hippel-Lindau (VHL) disease, caused by germline mutations in the VHL gene, is a hereditary tumor syndrome manifested by hemangioblastomas, clear cell renal cell carcinomas, and pheochromocytomas. In addition, a multitude of other rare tumors, including parasympathetic paragangliomas, can occur and even be the sole manifestation of VHL disease. The VHL gene is a bona fide tumor suppressor gene with biallelic inactivation contributing to tumor formation. However, in parasympathetic paragangliomas occurring in VHL disease, biallelic inactivation of the VHL gene has not been demonstrated to date. Design: The head and neck paragangliomas of two VHL patients were analyzed for mutations by direct sequencing of the VHL gene. In addition loss of heterozygosity analysis was performed for three microsatellite loci near the VHL gene. To rule out other underlying genetic causes of the parasympathetic paragangliomas, mutation analysis of the SDHB, SDHC, and SDHD genes was also performed. Results: Apart from germline VHL mutations, no additional mutations were found in the paraganglioma-related tumor suppressor genes SDHB, SDHC, and SDHD. Analysis of paraganglioma tissue revealed loss of the VHL wild-type allele in both tumors, indicating that in these tumors biallelic VHL gene inactivation occurred. Conclusions: These findings indicate that parasympathetic paragangliomas in VHL disease, although rare, are part of the syndrome and related to VHL gene inactivation. Clinicians should be aware of the potential occurrence of parasympathetic paragangliomas in VHL disease. Copyright